tbuckley/cabot-search huggingface dataset:
Abstract 14839: Clinical, Polysomnographic and Echocardiographic Correlates of Excessive Daytime Sleepiness
Authors: Gul Jana Saeed, Ehimen Aneni, Fadar O Otite, Stephanie Thorn, Edward J Miller, Albert J Sinusas, Henry K Yaggi
Journal: Circulation (2022)

Introduction: Excessive Daytime Sleepiness (EDS) has been associated with adverse CVD outcomes. However, the mechanisms of elevated CVD risk in persons with EDS remains uncertain. In this study, we examined polysomnographic and echocardiographic correlates of EDS in a population of adults who underwent both sleep and cardiac stress tests. Methods: We analyzed data from 264 participants who had an in-lab polysomnogram (PSG) and a cardiac stress test between 2016 and 2019. All patients completed the Epworth Sleepiness Scale (ESS) questionnaire. EDS was categorized into 3 groups no EDS (ESS&lt;10), non-severe EDS (ESS 10-14), and severe EDS (ESS ≥15). T90%, the percentage of sleep time spent with oxygen desaturation &lt; 90%, was categorized into severe (≥ 20%) and non-severe nocturnal hypoxemia (&lt;20%). We assessed the relationship between EDS and CV risk factors, and EDS and echocardiographic parameters of diastolic dysfunction such as the E/e’, E/A ratio, left atrial volume index, tricuspid regurgitation jet velocity, and systolic function (ejection fraction, EF). Results: The mean age (SD) of the participants was 59 (11) years, and 59% were female. In logistic regression analysis severe EDS was associated with &gt;3-fold odds of a history of stroke or TIA [a OR 3.2 (95%CI:1.2-8.2), P=0.017] and nearly 4 times the odds of severe nocturnal hypoxemia [aOR 3.8 (95%CI: 1.7-8.6, P=0.002] compared to those with no EDS. We found no other association between EDS and demographic or CV characteristics or PSG variables. In the subset of patients with available echocardiogram data (n=199 - 213), there was no association between EDS and EF or echocardiographic parameters of diastolic dysfunction. Conclusions: EDS is strongly associated with severe nocturnal hypoxia and a history of stroke or TIA in adults with OSA. Further studies are needed to characterize the relationship between EDS and CVD.
Abstract 13764: Renalase Peptide Agonist Therapy Normalizes the Cardiac Response to Pressure Overload in Chronic Kidney Disease
Authors: Govind Krishna Kumar Nair, Jiasheng Zhang, Xiaojia Guo, nicole guerrera, Xiaohong Wu, Xiaoyue Hu, Fred S Gorelick, Robert Safirstein, Frank J Giordano, Lawrence H Young, Gary V Desir
Journal: Circulation (2022)

Introduction: Chronic kidney disease (CKD) increases susceptibility to heart disease. The mechanisms remain unclear and may include dysregulation of autocrine, paracrine or circulating factors. Renalase (RNLS) is a secreted protein expressed in the kidney and heart with potent pro-survival and anti-inflammatory properties. Cardiac pressure overload by transverse aortic constriction (TAC) is associated with increased cardiac RNLS expression in normal mice, while mice with CKD have decreased cardiac RNLS. We hypothesized that CKD would alter the hypertrophic response to TAC, and that therapy with exogenous mouse-specific RNLS agonist peptide (mRNLS-ap) would normalize the response. Methods: In wild-type male C57BL/6J mice, CKD was induced by two doses of cisplatin (15mg/kg SQ), two weeks apart (validated and published CKD model). Non-CKD mice received 0.9% saline. TAC was induced 8 weeks after first cisplatin dose. Control mice (sham) had aortic arch exposure without constriction. mRNLS-ap (20 mg/kg SQ) was injected twice daily for 14 days, starting one day before surgery. Serial echocardiograms were performed. Results: CKD groups had similar degrees of renal failure. Mean aortic gradients were comparable after TAC. Kidney RNLS protein expression was 44% less in CKD (n=8) than non-CKD (n=4) mice at sacrifice (12 weeks after surgery) (p&lt;0.001). One-week post-surgery, untreated CKD-TAC mice showed impaired hypertrophy with smaller increase (over baseline pre-TAC values) in LV wall thickness than non-CKD-TAC mice (15 ± 5% vs. 35 ± 4%, n=12 each; p&lt;0.001). Four weeks post-surgery, the response normalized with similar LV wall thickness increases in CKD-TAC and non-CKD-TAC mice (31 ± 8% vs. 29 ± 3%, n=11-12 each; p&gt;0.99). Sham groups did not change. One-week post-surgery with exogenous mRNLS-ap therapy, the difference in LV wall thickness increase between the CKD-TAC and non-CKD-TAC hearts was eliminated (28 ± 6%, n=9 vs. 24 ± 8%, n=4; p&gt;0.95). Sham groups did not change. Conclusions: RNLS expression is reduced in cisplatin-induced CKD, and associated with a delayed LV hypertrophic response to TAC. RNLS agonist therapy corrects this delay. Plasma and/or cardiac RNLS are important early mediators of cardiac adaptation to pressure overload stress in CKD.
Abstract 14359: Impact of Marital Stress on 12-month Health Outcomes Among Young Adults With Acute Myocardial Infarction
Authors: Cenjing Zhu, Rachel P Dreyer, Fan Li, Erica S Spatz, Cesar Caraballo, Shiwani Mahajan, Valeria Raparelli, Erica C Leifheit, Yuan Lu, Harlan M Krumholz, John Spertus, Gail DONOFRIO, Louise Pilote, Judith H Lichtman
Journal: Circulation (2022)

Background: Psychosocial stress is associated with worse cardiac outcomes, but little is known about the prognostic impact of marital stress in young adults (≤55 years) with acute myocardial infarction (AMI). We investigated the association between marital stress and 1-year health outcomes in young AMI survivors. Methods: We used data from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), which enrolled people aged 18-55 years with AMI (2008-2012). Marital stress was assessed among married/partnered participants at 1 month post-AMI using the Stockholm Marital Stress Scale, categorized as absent/mild, moderate, and severe. Main outcomes were physical/mental health status, generic/disease-specific quality of life, angina, depressive symptoms, and all-cause readmission at 1 year post-AMI. Linear and logistic regression models were sequentially adjusted for baseline health status, demographics, and socioeconomic factors (including education level, income level, employment status, and insurance status). Results: Among the 1593 married/partnered participants in our study, more women reported severe marital stress than men (39.4% vs 30.4%, p=0.001). Having severe marital stress was associated with worse physical and mental health, lower generic and cardiovascular-specific quality of life, more angina and depressive symptoms, and 1.48 times higher all-cause readmission at 1 year post-AMI. These associations remained significant after adjusting for baseline health score and patient demographics ( Table Model 1 ), but they attenuated and became non-significant when further adjusting for socioeconomic factors ( Model 2 ). Conclusion: Marital stress was associated with worse health outcomes in young AMI patients, which can be partially mediated by socioeconomic factors. Further research is needed to understand this complex relationship and potential causal pathway associated with these findings.
Abstract 13590: The Fick Method With Lafarge Estimates of Oxygen Consumption Systematically Over-Estimates Cardiac Index When Compared to Thermodilution in Children
Authors: Andrew A Lawson, Paul Tannous, Christina Laternser, Karl Migally
Journal: Circulation (2022)

Introduction: There are known sources of error in cardiac index calculated by the Fick method with LaFarge estimates of oxygen consumption (eFick CI) and in cardiac index measured by thermodilution (TDCI). In a large adult cohort, there was only modest correlation between eFick CI and TDCI. Hypothesis: Among pediatric patients undergoing cardiac catheterization, eFick CI and TDCI will differ by greater than 20% in greater than 10% of cases. Methods: We performed a single-center retrospective chart review of patients aged 3-18yrs who underwent cardiac catheterization with documented eFick CI and TDCI from 2004 to 2020. eFick CI was calculated using oxygen consumption estimated by the LaFarge equation. Results: Among 201 right heart catheterizations (mean age 12.2 yrs, SD 4.4yrs; 51% male) performed on 161 distinct patients, the most frequent diagnosis was cardiomyopathy, followed by congenital heart disease, and pulmonary hypertension. TDCI and eFick differed by &gt;20% in 49% of catheterizations; further, eFick CI was systematically higher than TDCI, with mean difference +0.71L/min/m 2 , SD 1.07L/min/m 2 . In a multivariate linear regression analysis (Table 1), higher mean CI ((eFick CI + TDCI)/2), and older age were predictive of greater percent difference between eFick CI and TDCI; for each increase in mean CI by 1.0 L/min/m 2 , the expected percent difference in CI increased by 9.9% (p=0.000). Conclusions: In pediatric patients undergoing cardiac catheterization, eFick CI is systematically higher than TDCI and the difference between values is frequently &gt;20%, which may have clinically significant implications. Discrepancies between eFick CI and TDCI increase at higher mean CI.
Abstract 13097: Safety, Pharmacokinetics, and Pharmacodynamics of AZD3366 Alone and in Combination With Aspirin and Ticagrelor in Healthy Subjects
Authors: Dimitris Kardassis, Ann-Charlotte Egnell, Magnus Åstrand, Samuel J Daniels, Celeste Frickleton, Carl Whatling, Ola Fjellstrom, Anders Gabrielsen
Journal: Circulation (2022)

Introduction: Despite reperfusion in patients with ST-elevation myocardial infarction and acute ischemic stroke; reperfusion injury, microvascular dysfunction, thrombosis, and obstruction remain important causes of persistent ischemia and infarct expansion leading to poor clinical outcome. AZD3366, a recombinant human apyrase engineered to enhance hydrolysis of extracellular adenosine tri-/diphosphate (ATP/ADP) to adenosine monophosphate and subsequently adenosine, has exhibited anti-thrombotic, anti-inflammatory, and tissue protective properties in preclinical studies. Methods: In this phase 1 randomized single-blind placebo-controlled study in healthy subjects ( NCT04588727 ), 7 cohorts of 8 subjects received a single short IV infusion of AZD3366 (2-640 mg [n=6]) or placebo (n=2). A further 3 cohorts of 5 healthy Japanese/1 cohort of 8 healthy Chinese subjects were included within this dose range. A separate group of 24 subjects received 160 mg of AZD3366 in combination with aspirin and ticagrelor (n=12) or aspirin and ticagrelor alone (n=12). The primary objective was to assess safety and tolerability; secondary objectives included assessment of pharmacokinetics (PK) and pharmacodynamics of AZD3366. Results: Overall, 103 subjects were randomized; mean age 37.2 (± 9) years, 100 were male. AZD3366 treatment alone or in combination with ticagrelor and aspirin did not result in any clinically relevant safety or tolerability findings. Peak AZD3366 plasma concentrations were reached within 0.5 h post-dosing, followed by monophasic or biphasic decline with a terminal PK half-life of approximately 140 h. Complete ADP-stimulated platelet aggregation inhibition was reached within 10 mins post-dosing; duration ranged from 4 h at 2 mg to ~35 days at 640 mg (Figure). Conclusions: AZD3366 alone or in combination with aspirin and ticagrelor was generally safe, well tolerated, and achieved complete platelet inhibition with a dose-dependent duration.
Abstract 12836: Cardiovascular Disease Profile in Children With Hcm (aspire-hcm): A Canadian Cross-Sectional Study
Authors: Jennifer Conway, Tara Pidborochynski, Michael Khoury, Santokh S DHILLON, Laurence Vaujois, Frederic Dallaire, Kathryn Armstrong, Daryl Schantz, Wadi Mawad, Nassiba Alami Laroussi, Timothy J Bradley, Aamir Jeewa
Journal: Circulation (2022)

Introduction: Adults with hypertrophic cardiomyopathy (HCM) have been shown to have abnormal cardiovascular (CV) health, leading to long-term problems. However, little is known about the CV health of children with HCM. Given the emphasis placed on physical activity restrictions in patients with HCM, effective communication regarding the importance of a heart-healthy lifestyle may be lacking. Therefore, the aim of this study was to assess CV health in a cohort of children with HCM across Canada. Methods: Children with HCM, ages 10-18 years old, were recruited from 10 Canadian sites and underwent CV health screening including: body mass index (BMI), central adiposity assessment via the waist-to-height ratio (WHtR, ≥0.5 considered abnormal), non-fasting lipid profile, (abnormal cholesterol being &gt;4.4 mmol/L); systolic blood pressure (≥95th percentile considered hypertensive;0 and a 2-week period of activity assessment using a wrist Fitbit. An average daily step count ≥12,500 was used as a surrogate for ≥60 minutes of moderate to vigorous physical activity. Results: Forty-six patients with HCM were included [76% male; median age 15.4 years (IQR 13.7, 16.7)]. The median BMI percentile was 85.0 (IQR 58.5, 97.0) with 56.6% being overweight or obese (BMI &gt;85th percentile). The WHtR was a median of 0.51 (IQR 0.43-0.55), with 55.6% being ≥0.50. The median systolic blood pressure was 113.5 mmHg (IQR 101.8-123.0), with 10.8% having measurements in the hypertensive range. The median cholesterol was 3.7 mmol/L (IQR 3.4-4.4), with 29% of patients having an elevated cholesterol. Average daily step count ≥12,500 occurred in 14% of the cohort with the median average steps per day being 7,590 (IQR 5,205-10,894). Conclusions: The majority of Canadian children with HCM have evidence of physical inactivity and an adverse CV risk profile. In order to prevent poor CV health outcomes in adulthood, interventions are required to target these risk factors in children with HCM.
Abstract 14074: Unique Circulating microRNA Profile in Pediatric Heart Transplant Recipients
Authors: Shelley D Miyamoto, Ashley Pietra, Brian D Feingold, Bonnie Neltner, James D Wilkinson, Anis Karimpour-Fard, Steven A Webber, Carmen C Sucharov
Journal: Circulation (2022)

Introduction: MicroRNAs (miRs) are small noncoding RNAs capable of modulating the expression of many genes. Hypothesis: Our hypothesis was that circulating miRs would be a biomarker of acute cellular rejection (ACR) in pediatric heart transplant recipients (PHTR). Methods: An array for 381 miRs was performed using serum from 52 PHTR and 21 healthy pediatric controls (HC). ACR was defined as ISHLT biopsy score ≥2R. Patients with antibody mediated rejection were excluded. RNA was extracted using the miRNeasy Mini Kit (Qiagen), and arrays were performed using the TaqMan Open Array miR panel (Thermo Fisher Scientific). Statistical analysis included Random Forest (RF) with area under the receiver operator curve (AUC) based on the top 3 differentiating miRs by RF, and Wilcoxon rank-sum t-test (significant q-value &lt; 0.05). Results: Of the 52 PHTR, median age 8.5 years, 44% female, race/ethnicity white in 83%, 12% African American, 13% Asian/other, and 13% Hispanic; 22 PHTR had ACR at time of serum collection. There were 21 HC, median age 5.6 years, 38% female, race/ethnicity white in 76%, 24% Asian/other, and 19% Hispanic. There were 66 miRs significantly different between HC and all PHTR (AUC of 0.91). For HC vs PHTR without ACR there were 50 differential miRs (AUC of 0.94), and for HC vs PHTR with ACR there were 51 differential miRs (AUC 0.96). Table 1 demonstrates miRs that are differentially expressed compared to HC based on the presence or absence of ACR. Circulating miRs were not different between PHTR with (n=22) and without ACR (n=30). Conclusions: The circulating miR profile of PHTR is unique compared to HC, suggesting a strong influence of the transplant mileu on miR expression. There were 17 miRs with differential expression compared to HC based on the presence or absence of ACR. These results support future investigations in larger populations to determine if circulating miRs could serve as biomarkers of ACR in PHTR, and whether these miRs contribute to the pathophysiology of ACR.
Abstract 14237: Left Atrial Dynamics Predict Incident Atrial Fibrillation in Hypertrophic Cardiomyopathy
Authors: Erik Andrews, Sarah Cuddy, Carolyn Ho, Neal K Lakdawala
Journal: Circulation (2022)

Introduction: Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM) and is associated with an 8-fold increased risk of stroke. However, the ability to predict incident AF remains limited. Methods: At a single referral center, we identified HCM patients with paired transthoracic echocardiograms (TTEs) performed at least 12-months apart and both prior to a diagnosis of AF. Baseline clinical characteristics and the occurrence of incident AF was obtained from a clinical registry and the electronic medical record. Comprehensive analysis of TTEs was performed by an experienced reader who was blinded to clinical events and included total atrial emptying fraction (LA EF) and its individual components, including LA volume at end-systole. Changes in parameters over time were determined by comparing results between each TTE. Univariate and multivariate regression, Cox proportional hazard, and Kaplan-Meier methods were used to analyze factors associated with the subsequent incidence of AF. Results: We studied 202 patients (mean age 45 years, 42% female, 27% hypertensive, 39% with sarcomere mutation, 37% NYHA II or greater). Of all factors examined, the initial LA EF, as well as the rate of LA remodeling as defined by the change in LA end-systolic volume over time, were most significantly predictive of AF development (Figure 1). These results were robust to multivariate regression with other factors significant in HCM (Figure 1C), including baseline LA diameter. Conclusions: Reduced LA function (the LA EF) and increased rate of LA dilation predict incident AF in HCM. Future studies are needed to identity factors associated with adverse LA dynamics in HCM and whether these can be mitigated with pharmacotherapy.
Abstract 12741: Effect of One Year of Exercise Training on Left Ventricular Relaxation in Patients With Stage B Heart Failure
Authors: Doruk Karaaslan, Satyam Sarma, Christopher Hearon, Katrin A Dias, Michinari Hieda, Benjamin D Levine, James P Macnamara
Journal: Circulation (2022)

Introduction: Left ventricular hypertrophy (LVH) is a risk factor for developing heart failure (HF). Exercise training decreases LV stiffness in individuals with LVH, but the effects of exercise training on LV relaxation in these individuals are unknown. Methods: Patients with LVH (&gt; 11 mm) and elevated cardiac biomarkers (N-terminal pro- B-type natriuretic peptide [&gt;40 pg/mL] or high-sensitivity troponin T [&gt;0.6 pg/mL]) were randomized 2:1 to 1 year of monitored exercise training 4-5 days a week, including high intensity intervals, and 1-2 days of strength training or an attention control. Isovolumetric relaxation time (IVRT) was measured with pulse wave Doppler echocardiography and pulmonary capillary wedge pressure (PCWP) was consecutively measured with right heart catheterization before and after intervention. LV relaxation time constant, Tau, was estimated by Tau = IVRT / (Ln End-systolic pressure (ESP) - Ln PCWP) (Figure). Maximal oxygen uptake (VO 2 Max; Douglas bags) was measured with an incremental treadmill test. LV Stiffness was significantly improved in exercise arm, previously reported. Results: Thirty-one participants completed the study (Control: n=11, 51±6 years, 55% men, Exercise: n=20 53±6, 65% men). VO 2 Max increased by 18.2% in the exercise arm (2.2±0.6 L/min to 2.5±0.6, but not in controls; group x time p&lt;0.001). Exercise training did not change Tau (exercise 38.2±6.5 to 39.8±8.7 ms) compared to control(40.3 ± 5.9 to 39.2±6.8 ms, group x time p = 0.84, Figure ). Exercise training resulted in no significant changes in IVRT (p = 0.35), SBP (p=0.89) or PCWP (p=0.69). Conclusions: In patients with LVH at risk for HF, one year of high intensity exercise training did not improve LV relaxation despite significant improvement in ventricular stiffness and exercise capacity. These results suggest the primary mechanism for HF risk reduction with exercise training is by lowering LV stiffness, and not necessarily altering LV relaxation.
Abstract 135: Regional Variation Of Adult Awareness Of And Likelihood To Perform Hands-only Cardiopulmonary Resuscitation
Authors: Melanie B Turner, Jose M Ferrer, Sachin Menon, Marida Straccia
Journal: Circulation (2022)

Introduction: About 75% of out-of-hospital cardiac arrests (OCHA) happen in the home. Based on US data, only about 40% of people who experience an OCHA receive bystander CPR before EMS arrives. Global community awareness data of Hands-Only CPR (HOCPR) and willingness to perform are limited. Objective: Determine global awareness of and likeliness to perform HOCPR among adults and examine regional variation. Methods: An online native language survey was administered among nationally representative samples of adults ≥18 years of age in 50 countries across 6 global regions. The survey was administered June-July 2021 using the YouGov RealTime omnibus service. The survey included one question regarding awareness of the concept of HOCPR as involving calling the local emergency number, and then pushing hard and fast in the center of the chest, but not involving breathing into the person’s mouth. A second question gauged willingness to perform HOCPR in an emergency on a 5-point scale. Participants were also able to answer “Don’t Know/Not Sure” to both questions. Results were weighted by country, then combined by region. Results: Of 47,488 adults (49.15% female), 66.79% reported awareness of HOCPR. Regional awareness ranged from 58.75% to 79.07%. Of those who were aware of HOCPR, 77.72% were extremely, very likely, or somewhat likely to give HOCPR in an emergency (regional range, 74.09% to 88.01%). Globally, awareness increased likeliness by 44.54%. In every region, there were no awareness differences between men and women (p=0.90); however, men were more likely than women to give HOCPR (p=0.02). Conclusions: Most respondents were aware of HOCPR. Those who were aware were more likely to give HOCPR to a bystander in an emergency. Likeliness to give HOCPR varies by global region. Efforts are needed in all regions to increase awareness and remove barriers that prevent people from helping OHCA victims.
Abstract 13146: Cardioprotective Effects of Mtss1 Reduction in Dilated Cardiomyopathy
Authors: Dongwook Choe, Jeffrey A Brandimarto, Nataliya Petrenko, Ingrid Marti-Pamies, Megan Burke, Wenjian Lv, Sharlene Day, Kiran Musunuru, Xiao Wang, Thomas P Cappola
Journal: Circulation (2022)

Introduction: MTSS1 is an I-BAR protein that interacts with the actin cytoskeleton and the cell membrane and is speculated to play a role in cell motility, tumor metastasis, and cardiogenesis. Enhancer variants that reduce the expression of MTSS1 in the human left ventricle have been associated with cardioprotective traits in genome-wide association studies. However, the effect of MTSS1 downregulation on the development of heart disease has not been studied in experimental models. Here we tested the hypothesis that reduction of MTSS1 protects against dilated cardiomyopathy (DCM) in vitro and in vivo. Methods: We used CRISPR-Cas9 to knock out MTSS1 in induced pluripotent stem cells (iPSCs) harboring pathogenic variants from patients with severe DCM. DCM iPSC lines with and without MTSS1 were then differentiated into cardiomyocytes and phenotyped in vitro. A DCM mouse model containing a TPM1 D230N transgene was crossed with a mouse model heterozygous for Mtss1 knockout. Progeny from this F1 cross were assessed for differences in cardiac structure and function via echocardiography. Results: MTSS1 deletion restored the beta-adrenergic response in DCM iPSC cardiomyocytes. In parallel, Mtss1 deletion partially rescued DCM-associated phenotypes including left ventricular dilation and reduced ejection fraction in mice. Conclusions: Our initial results suggest a causal link between MTSS1 reduction and cardioprotection in DCM. Inhibiting cardiac MTSS1 may hold therapeutic potential for DCM, though the cellular mechanisms through which MTSS1 affects cardiac phenotypes remain under investigation.